Paclitaxel is an approved drug for refactory advanced ovarian cancer, breast cancer and most recently AIDS-related Kaposi's sarcoma. It is a diterpene taxane found in very low concentration in the bark of Pacific yew tree Taxus brevifolia but its biogenetic precursor, 10-deacetylbaccatin, 10-DAB 1 is found in relatively much higher concentration. Because of complex structure of taxane nucleus, total synthesis routes are very long and tedious and therefore appear uneconomical compared to semisynthesis.
Since, there is great interest in the semisynthesis of paclitaxel to meet its growing demand; 10-DAB has emerged as a key raw material for synthesis of paclitaxel, docetaxel and their analogs.
A synthetic protocol for the conversion of 10-DAB into taxoal requires
a) selective acylation/protection at similarly reactive C-7 and C-10 hydroxyl groups. Among the 1,7,10 and 13-hydroxyl groups present in the 10-DAB, the order of reactivity is 7>10>13>1. Therefore, selective esterification of 13-hydroxyl requires protection of both 7 and 10-hydroxyl. If acetyl group at C-10 is required, as in the synthesis of paclitaxel, then 7-hydroxyl is to be protected first followed by acetylation at 10-hydroxyl.
b) selective esterification of C-13 hydroxyl group with a suitably protected N-benzoylphenylisoserine. It has been found that α-hydroxy-β-amidoacyl moiety at 13-hydroxyl of taxane is very essential for anticancer activity (Wani et al J.Am.Chem. Soc. 93, pp2325, 1971). Esterification at 13-hydroxyl is very sluggish due to its stereo-electronic disposition. Hence, the apparently simple reaction has become a very important step in assembling of the side chain and 13-hydroxytaxane. It is known from the literature that with cyclic forms of α-hydroxy-β-amidoalkylcarboxylic acid, the side chain precursors, esterification step proceeds to completion in high yield. Therefore, new cyclic forms of side chains, which give high yield of coupled product under simple reaction conditions without their use in large excess, are required to develop new semi-synthetic routes for paclitaxel and its analogs.
c) conversion of side chain precursor part into side chain and removal of protecting groups from baccatin part. These reaction conditions should be mild in nature affording the final material in high yield with very few side products. For successful commercial production, it is very much desired that the crude semi-synthetic taxane anticancer molecules should be produced with such purity that they could easily purified into pharmaceutical grade material. Because of very sensitive nature of taxane nucleus, it is highly prone to degradation and the desired semi-synthetic crude materials are often produced contaminated with structurally similar impurities, very difficult to separate completely.
Thus, it is obvious that new 13-hydroxytaxanes (more specifically 13-hydroxy-7,10-dihydroxyprotected-10-deacetylbaccatin and 13-hydroxy-7-hydroxyprotected baccatin) and the novel side chain precursors are sought for development of more facile routes of semisynthesis of taxane anticancer drugs.
As mentioned above, for esterification at 13-hydroxy, 7 and 10-hydroxy need to be protected/derivatised first. With this in view, we started exploring use of haloalkyl acid chlorides 2 as protecting groups for both 7 and 10 hydroxy. These protecting groups undergo hydrolysis faster than unsubstituted alkyl acid chlorides. Therefore, it is possible to deprotect these groups without many side products in presence of acetyl group under same condition. We have actually found that haloalkyl acid chlorides such as 1-halo/2,2-dihaloacyl chlorides can be used for selective protection and deprotection in taxane. Thus we have found 7-O-(2-haloacyl)baccatin and 7,10-O-di-(2-haloacyl)-10-DAB and similar haloacyl protected-taxanes as new types of intermediates for synthesis of taxanoid anticancer drugs, more specifically paclitaxel and docetaxel. 
In order to develop such side chain precursor which can produce paclitaxel/docetaxel after joining with taxane under very mild and preferably neutral condition, it was found that oxazolidine carboxylic acid 3 is a suitable side chain precursor. These side chain precursors have (alk-2-ynyloxy) carbonyl group as nitrogen protecting group. This group is cleaved under neutral conditions; therefore degradation of taxane can be avoided. The other N,O-bifunctional protecting group then undergoes cleavage very fast without any degradation under very mild condition. Most of the nitrogen protecting groups used so far either require harsh acidic conditions or hydrogenolysis for their removal. Therefore, these 3-(alk-2-ynyloxy) oxazolidines have emerged as new type of side chain precursors.
Herein we have described new intermediates for taxanoid anticancer drugs, their process of synthesis and process for synthesis of paclitaxel and similar analogs using them in (Scheme-1). 